ABSTRACT
Drosophila melanogaster expressing amyloid-ß42 (Aß42) transgenes have been used as models to study Alzheimer's disease. Various Aß42 transgenes with different structures induce different phenotypes, which make it difficult to compare data among studies which use different transgenic lines. In this study, we compared the phenotypes of four frequently used Aß42 transgenic lines, UAS-Aß422X , UAS-Aß42BL33770 , UAS-Aß4211C39 , and UAS-Aß42H29.3 . Among the four transgenic lines, only UAS-Aß422X has two copies of the upstream activation sequence-amyloid-ß42 (UAS-Aß42) transgene, while remaining three have one copy. UAS-Aß42BL33770 has the 3' untranslated region of Drosophila α-tubulin, while the others have that of SV40. UAS-Aß4211C39 and UAS-Aß42H29.3 have the rat pre-proenkephalin signal peptide, while UAS-Aß422X and UAS-Aß42BL33770 have that of the fly argos protein. When the transgenes were expressed ectopically in the developing eyes of the flies, UAS-Aß422X transgene resulted in a strongly reduced and rough eye phenotype, while UAS-Aß42BL33770 only showed a strong rough eye phenotype; UAS-Aß42H29.3 and UAS-Aß4211C39 had mild rough eyes. The levels of cell death and reactive oxygen species (ROS) in the eye imaginal discs were consistently the highest in UAS-Aß422X , followed by UAS-Aß42BL33770 , UAS-Aß4211C39 , and UAS-Aß42H29.3 . Surprisingly, the reduction in survival during the development of these lines did not correlate with cell death or ROS levels. The flies which expressed UAS-Aß4211C39 or UAS-Aß42H29.3 experienced greatly reduced survival rates, although low levels of ROS or cell death were detected. Collectively, our results demonstrated that different Drosophila AD models show different phenotypic severity, and suggested that different transgenes may have different modes of cytotoxicity. Abbreviations: Aß42: amyloid-ß42; AD: Alzheimer's disease; UAS: upstream activation sequence.
